Document Detail

Long-term potentiation requires activation of calcium-independent phospholipase A2.
MedLine Citation:
PMID:  8549755     Owner:  NLM     Status:  MEDLINE    
The predominant phospholipase activity present in rat hippocampus is a calcium-independent phospholipase A2 (302.9 +/- 19.8 pmol/mg.min for calcium-independent phospholipase A2 activity vs. 14.6 +/- 1.0 pmol/mg.min for calcium-dependent phospholipase A2 activity). This calcium-independent phospholipase A2 is exquisitely sensitive to inhibition by the mechanism-based inhibitor, (E)-6-(bromomethylene)-tetrahydro-3-(1-naphthalenyl)-2H-pyran -2-one (BEL). Moreover, treatment of hippocampal slices with BEL prior to tetanic stimulation prevents the induction of LTP (40.8 +/- 5.6% increase in excitatory post-synaptic potential (EPSP) slope for control slices (n = 6) vs. 5.8 +/- 8.5% increase in EPSP slope for BEL-treated slices (n = 8)). Importantly, LTP can be induced following mechanism-based inhibition of phospholipase A2 by providing the end product of the phospholipase A2 reaction, arachidonic acid, during the application of tetanic stimulation. Furthermore, the induction of LTP after treatment with BEL is dependent on the stereoelectronic configuration of the fatty acid provided since eicosa-5,8,11-trienoic acid, but not eicosa-8,11,14-trienoic acid, rescues LTP after BEL treatment (37.6 +/- 16.1% increase in EPSP slope for eicosa-5,8,11-trienoic acid vs. -3.7 +/- 5.2% increase in EPSP slope for eicosa-8,11,14-trienoic acid). Collectively, these results provide the first demonstration of the essential role of calcium-independent phospholipase A2 in synaptic plasticity.
M J Wolf; Y Izumi; C F Zorumski; R W Gross
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  FEBS letters     Volume:  377     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  1995 Dec 
Date Detail:
Created Date:  1996-02-21     Completed Date:  1996-02-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  358-62     Citation Subset:  IM    
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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MeSH Terms
Arachidonic Acid / pharmacology
Arachidonic Acids / pharmacology
Calcium / metabolism*
Enzyme Activation
Hippocampus / enzymology*
Long-Term Potentiation / physiology*
Naphthalenes / pharmacology
Phosphodiesterase Inhibitors / pharmacology
Phospholipases A / antagonists & inhibitors,  metabolism*
Phospholipases A2
Pyrones / pharmacology
Reg. No./Substance:
0/Arachidonic Acids; 0/Naphthalenes; 0/Phosphodiesterase Inhibitors; 0/Pyrones; 149301-79-1/arachidonyltrifluoromethane; 506-32-1/Arachidonic Acid; 7440-70-2/Calcium; 88070-98-8/6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; EC 3.1.1.-/Phospholipases A; EC A2

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